Design, synthesis and biological evaluation of new 2,5-diaryl-1,3,4-oxadiazole derivatives as selective cyclooxygenase-2 inhibitors Novel 2,5-diaryl-1,3,4-oxadiazole derivatives as selective cyclooxygenase-2 inhibitors
International Pharmacy Acta,
Vol. 4 No. 1 (2021),
2 June 2021
Non- steroidal anti - inflammatory drugs (NSAIDs) are common prescribed medications worldwide for the treatment of inflammatory conditions and pain. However, adverse effects of NSAIDs in long term use have led to investigation of selective cyclooxygenase - 2 (COX-2) inhibitors with reduced adverse reactions, including
gastrointestinal and cardiovascular side effects and nephrotoxicity.
Methods and Results:
In this study, a series of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel selective inhibitors of COX-2 were rationally designed, synthesized, and biologically evaluated. The structures of compounds were confirmed with LC-Mass, IR, and 1H NMR spectra. Based on our results, most of the compounds had proper inhibitory activity against COX-2 similar to celecoxib, and exhibited selectivity towards COX-2 than COX-1. In this series, compound 5f, with nitro group in the R position, revealed the highest inhibitory activity and selectivity (IC50 = 19.6 µM, SI = 108.88) against COX-2. The docking study of compound 5a showed that this structure had appropriate affinity to the active site of the enzyme forming multiple hydrogen bonds.
In summary, these structures will be a valuable lead scaffold to develop new potent and selective COX-2 inhibitors.
- Biological evaluation
- COX-2 inhibitors
How to Cite
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